Combined chemotherapy with gemcitabine and carboplatin for metastatic urothelial carcinomas in patients with high renal insufficiency.

BACKGROUND: This was a retrospective study to evaluate the activity and toxicity of a combined chemotherapeutic regimen of gemcitabine and carboplatin (GCa) in patients with metastatic urothelial carcinomas (UCs) with special regard to patients with highly impaired renal function. METHODS: Eleven patients whose creatinine clearance was 30 ml/min or under and who had been diagnosed with metastatic UC were treated with GCa. The patient cohort comprised 4 males and 7 females, with a median age of 74 (range 67-84) years. The median follow-up was 19 (range 1-58) months. RESULTS: Five of the 11 patients (45%) showed an objective response, with 2 achieving a clinically complete response and 3 a partial response with GCa. The grade 3/4 toxicity of the regimen was primarily hematological, including anemia (55%), neutropenia (45%), and thrombocytopenia (45%). Four patients (36%) could not complete the treatment in total. Grade 3 pneumonitis was found in one patient, and the treatment was terminated. Grade 4 febrile neutropenia occurred in the patient on hemodialysis, and the patient was forced to discontinue the chemotherapy. Another 2 patients also called off the treatment due to a pulmonary adverse event and an elevation of serum creatinine, respectively. CONCLUSIONS: GCa appears to be effective for the treatment of metastatic UCs in patients with impaired renal function, but it is necessary to pay attention to the occurrence of severe adverse events.

[Low-dose docetaxel in combination with dexamethasone for hormone-refractory prostate cancer].

PURPOSE: Efficacy and tolerability of docetaxel-based chemotherapy against hormone-refractory prostate cancer (HRPC) has been shown lately. The objective of this study was to evaluate retrospectively the efficacy and toxicity of low-dose docetaxel in combination with dexamethasone. PATIENTS AND METHODS: Sixteen patients, with a median age of 69.5 years (range 54-85 years), diagnosed with HRPC were administered a treatment regimen consisting of docetaxel (60-80 mg/body or 50 mg/m2) once every 3 or 4 weeks and dexamethasone 1 mg daily at our institution between November, 2004 and March, 2010. RESULTS: The patients received a median of 11.5 cycles of treatment (range, 2-35 cycles). Eleven of 16 patients (68.8%) had a > or = 50% decrease in serum prostate-specific antigen. The median progression-free survival and overall survival times were 7.1 and 20.3 months, respectively. Grade 3 neutropenia occurred only in 2 patients. Infective endocarditis, gastrointestinal or cerebral hemorrhage, and compressive fracture were occurred in each patient. CONCLUSIONS: The combination of low-dose docetaxel every 3-4 weeks and dexamethasone daily was effective and well tolerated in patients with HRPC. However, it is necessary to pay continuous attention to side effects due to the frequent presence of comorbid diseases particularly in the elderly.

Long-term results of combined chemotherapy with gemcitabine and cisplatin for metastatic urothelial carcinomas.

BACKGROUND: This retrospective study aimed to determine the long-term effects and toxicity of a combined chemotherapeutic regimen of gemcitabine and cisplatin (GC) in the treatment of metastatic urothelial carcinomas (UCs). METHODS: Seventy-one patients with metastatic UC were treated with GC (gemcitabine 1000 mg/m(2) on days 1, 8, and 15 and cisplatin 70 mg/m(2) on day 2 every 28 days). The patients were divided into 3 groups: patients who had not undergone prior chemotherapy (group 1), patients who relapsed more than 6 months after being treated with the prior cisplatin-based regimen (group 2), and patients in whom the prior cisplatin-based regimen demonstrated no effect (group 3). The median follow-up was 42 months. RESULTS: In group 1, 20 of the 32 patients (63%) showed an objective response, with 6 achieving a clinically complete response (CR) and 14 a partial response (PR) with GC. Ten of 32 patients (31%) and 1 of 7 patients (14%) showed objective responses in groups 2 and 3, respectively. Patients in group 2 who had previously been treated with regimens other than GC showed a better objective response (58%) than those with GC (15%). The median time to progression in group 1 was 6 months, and the median overall survival was 14 months. In all, the nonhematological toxicities associated with GC were quite mild. Grade 3-4 toxicity was primarily hematological, including anemia (19%), neutropenia (36%), and thrombocytopenia (42%). CONCLUSIONS: GC is therefore considered to be a highly effective and well-tolerated regimen with moderate toxicity for the treatment of metastatic UCs.

[Case report: simultaneous bilateral testicular tumors with different cell types].

A 29-year-old man was admitted to our hospital due to bilateral testicular tumors. The bilateral testicular tumors were palpated and visualized by ultrasound and magnetic resonance imaging (right 8 cm, left 6 cm in diameter). Bilateral high orchiectomies were performed after frozen storage of the sperm. Pathological examination revealed seminoma and immature teratoma in the right testis and seminoma in the left testis. Three months later, computed tomography (CT) showed multiple metastatic lung nodules. In addition, positron emission tomography (PET)-CT examination revealed peri-caval lymph node metastasis together with the lung metastases. Lung metastases disappeared, but the lymph node metastasis reduced and remained after 3 courses of combination chemotherapy with bleomycin, etoposide and cisplatin. PET-CT examination revealed that no uptake of FDG was seen in the lung and lymph nodes. Retroperitoneal lymph node dissection was performed. No viable tumor cells were histologically present in the excited lymph nodes. The postoperative course was good and uneventful at 10 months under androgen replacement therapy without disease recurrences.

[Intrascrotal rhabdomyosarcoma in adult: a case report].

The patient was a 34-year-old man presenting with the right intra-scrotal painless mass. With a diagnosis of right intrascrotal tumor, the patient underwent right high orchiectomy. The pathological diagnosis of pleomorphic rhabdomyosarcoma arisen from the right spermatic cord was made. Computed tomography revealed a single metastasis in the para-vena cava lymph node. Systemic chemotherapy with vincristine, actinomycin D, plus cyclophosphamide (VAC therapy), and etoposide plus cisplatin (EP therapy) were made according to Intergroup Rhabdomyosarcoma Study (IRS)-IV Regimen 45. But the chemotherapy was ineffective and a retoroperitoneal lymphadenectomy (RPLND) was therefore performed. After 3 months following RPLND, the tumor relapsed in a pelvic lymph node involved in right ureter and ileocaecal valve. Resection of the tumor with ileocaecum was performed and then intraoperative radiotherapy (15 Gy) against the tumor bed was performed to ensure the curative effects. After his recovery, he received a total of 6 courses of systemic chemotherapy consisting of vincristin, ifosphamide, etoposide (IRS-IV Regimen 47). The patient was rigorously followed up for 42 months after the final chemotherapy, with no tumor recurrence.

[Fluvastatin induces apoptosis on human tongue carcinoma cell line HSC-3].

Statins, which are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, suppress cell proliferation and induce apoptosis in various cancer cell lines. However, the effects of statins in head and neck carcinoma have not been reported. In this study, we investigated the mechanism by which fluvastatin induces apoptosis in HSC-3 cells. An increase in caspase-3 activity was observed. The apoptosis induced by fluvastatin was inhibited by the addition of geranylgeranyl pyrophosphate (GGPP) to the cell culture. When we examined the survival signals at the time of apoptotic induction, we also found that fluvastatin had caused a remarkable decrease in the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Moreover, we also found that U0126, a MEK1/2 inhibitor, induces apoptosis in HSC-3 cells. These results suggested that fluvastatin induces apoptosis by inhibiting GGPP biosynthesis and consequently decreasing the level of phosphorylated ERK1/2. The results of this study also indicate that fluvastatin may be used as an anticancer agent for tongue carcinoma.

[Clinical evaluation of biapenem for febrile neutropenia in patients with hematological disorders].

We examined the clinical evaluation of biapenem (BIPM) for febrile neutropenia in patients with hematological disorders. BIPM was administrated by drip infusion when fever developed over 37.5 degrees C with a neutrophil counts lower than 1000/microl. The underlying diseases were acute myelogenous leukemia in 16 cases, acute lymphocytic leukemia in 1, malignant lymphoma in 14, myelodysplastic syndrome in 1, aplastic anemia in 1. Microbiologically documented infections were found in 3 cases (9.1%) before treatment. Clinical effect was excellent in 9 cases, good in 11, fair in 6, poor in 7. Factors associated with efficacy rate were concomitant use of granulocytecolony stimulating factor, duration of neutropenia and neutrophil counts at day 3 of day after start of the therapy. No serious adverse events were observed in all cases, although one case developed exanthema. In conclusion, these results confirmed the efficacy and safety of BIPM for febrile neutropenia in patients with hematological disorders.

[Clinical analysis of HLA-DR-negative non-M3 AML].

The type of leukemia was defined as HLA-DR(-) non-M3-AML, when HLA antigens were detected by flow cytometry at an incidence of < 20% of the blast population excluding M3-AML. Out of 109 patients with de novo acute myeloid leukemia, 8 patients had HLA-DR(-) non-AML-M3. According to the French-American-British criteria, 7 patients could be subdivided into 3 patients with M1, 4 patients with M2 and 1 patient with M4. The morphological features of bone marrow aspiration demonstrated no dysplasia and peroxidase stain positivity was noted in over 86% of the blast cells in all patients, the blast cells with fine granularity in 7 patients. The cytogenetic analysis revealed a normal karyotype. There was no expression marker of the blast antigens except CD13, CD14, CD33, CD34 and CD56. All of 7 patients who underwent induction therapy attained complete remission. Overall survival and disease-free survival showed no significant differences between the HLA-DR(-) non- M3-AML group and the HLA-DR(+) AML group.

Mitochondrial DNA mutations and 8-hydroxy-2'-deoxyguanosine Content in Japanese patients with urinary bladder and renal cancers.

BACKGROUND: Several recent studies have demonstrated the presence of mitochondrial DNA (mtDNA) mutations in various human cancers. The origin of these mutations may be attributable to oxidative damage from reactive oxygen species (ROS). In order to investigate the relationship between mtDNA mutations and ROS in human cancers, urinary bladder and renal cancers were examined for mutations in the displacement-loop (D-loop) region of mtDNA and for 8-hydroxy-2'-deoxyguanosine (8-OHdG) content. MATERIALS AND METHODS: The D-loop region of mtDNA of Japanese patients with urinary bladder or renal cancers was examined by direct sequencing. The level of 8-OHdG was measured in the patients who had undergone radical cystectomy or nephrectomy from excised specimens. RESULTS: Somatic mutations in the D-loop region were detected in 7 (23%) out of 31 patients with bladder cancer and 3 (14%) out of 21 patients with renal cancer. The most frequent mutations were in the poly(C) mononucleotide repeat located at positions 303 to 309. The levels of 8-OHdG in cancer tissues were significantly higher than in the neighboring non-cancerous tissues, but many of the cancers with an elevated 8-OHdG level did not display D-loop mutations. CONCLUSION: These results suggest that the D-loop region of mtDNA might have a genetic instability in cancer tissues independently from the 8-OHdG level.

[Gemcitabine and cisplatin therapy in advanced or metastatic urothelial cancer: comparison of side effect with MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin)].

OBJECTIVE: Cisplatin-based combination chemotherapy has been considered as standard therapy for advanced or metastatic urothelial carcinoma. A recent study has, however, revealed that gemcitabine may have the potential to act synergistically with cisplatin. Therefore, the side effects of gemcitabine plus cisplatin (GC) therapy were compared with those of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) therapy in patients with advanced or metastatic urothelial carcinoma. PATIENTS AND METHODS: Twenty-two patients received GC therapy. Gemcitabine (1000 mg/m2) was administered on days 1, 8 and 15 of each 28-day cycle. Cisplatin (70 mg/m2) was administered on day 2 of each cycle. As a control group, 24 patients received MVAC therapy (methotrexate at 30 mg/m2 on days 1, 15, 22, vinblastine at 3 mg/m2 on days 2, 15, 22, doxorubicin at 30 mg/m2 on day 2, and cisplatin at 70 mg/m2 on day 2 of each 28-day cycle. RESULTS: In the group of patients which received GC therapy, the overall response rates based on independent radiologic reviews of the 20 patients with measurable disease were 55%, with 20% CR and 35% PR. Fewer GC patients as compared with MVAC patients had grade 3/4 anorexia (4.5% vs. 75%, respectively), stomatitis (9.0% vs. 66.7%, respectively), and alopecia (27.3% vs. 100%, respectively). On the other hand, there were no significant differences in the incidence or pattern of hematologic toxicities between the group receiving GC therapy and that receiving MVAC therapy. Fatal neutropenic sepsis occurred in one patient receiving MVAC therapy. CONCLUSION: GC therapy is effective for the treatment of advanced or metastatic urothelial carcinoma, with an acceptable clinical safety profile. This study also indicates that GC therapy may be better tolerated and safer than MVAC therapy.

[A case of small cell carcinoma in the urinary bladder responding to gemcitabine/cisplatin combination therapy as neoadjuvant chemotherapy].

We report a case of primary small cell carcinoma of the urinary bladder. A 79-year-old man with the chief complaints of macrohematuria and pollakisuria was admitted to our hospital. Cystoscopy and computed tomography (CT) revealed a non-papillary broad-based bladder tumor. Histological diagnosis was small cell carcinoma of the urinary bladder, and he underwent 3 courses of neoadjuvant chemotherapy including gemcitabine and cisplatin with a preoperative diagnosis of cT3bN0M0. After the chemotherapy, cystoscopy and CT showed complete remission. Total cystectomy with ileal conduit was performed following 3 courses of chemotherapy. Microscopic examination revealed that the small cell carcinoma had disappeared and the converted squamous cell carcinoma remained only in a small part of the specimens. The patient was carefully followed for 10 months after operation, with no tumor recurrence.

[Evaluation of prophylactic use of lamivudine in HBV-positive patients with malignant lymphoma undergoing chemotherapy].

A prospective evaluation was carried out on the effect of lamivudine administration as a prophylactic measure to prevent exacerbation of hepatitis in HBV carrier or chronic hepatitis B patients with malignant lymphoma undergoing chemotherapy. Eighteen patients were registered between 1997 and 2002 from institutions of the Research Group for the Treatment of Malignant Lymphoma. The patients' median age was 53 years old (39-73), and consisted of 8 males and 10 females. HBe-seroconversion had already occurred in 13 and liver biopsy had been performed in 8. No adverse effects of lamivudine were noted and the serum HBV-DNA content did not increase during lamivudine administration. Planned treatment courses could be completed in all patients. In 2, however, the viral load increased and the HBe antibody (Ab) value declined after the cessation of lamivudine, which were reversed to the normal ranges following the resumption of lamivudine. As for the overall outcome, 14 of the patients survived, and there were 4 fatalities due to malignant lymphoma. Serum HBeAb status may be regarded as a useful laboratory marker for deciding the safe cessation of lamivudine. An additional case is described, who had recovered from past HBV infection, but eventually succumbed to fulminant hepatitis after the cessation of lamivudine covering prolonged courses of chemotherapy. This illustrates a need for inclusion of such cases for the prophylactic use of lamivudine.

Performance of 11C-Pittsburgh Compound B PET Binding Potential Images in the Detection of Amyloid Deposits on Equivocal Static Images.

UNLABELLED: The goal of this study was to clarify whether binding potential (BP) images using (11)C-Pittsburgh compound B ((11)C-PiB) and dynamic PET can reliably detect cortical amyloid deposits for patients whose (11)C-PiB PET static images are ambiguous and whether visual ratings are affected by white matter retention. METHODS: Static and BP images were constructed for 85 consecutive patients with cognitive impairment after (11)C-PiB dynamic PET. Cortical uptake was visually assessed as positive, negative, or equivocal for both types of images. Quantitatively, the standardized uptake value ratio (SUVR) from the static image, the nondisplaceable BP from the dynamic image for mean gray matter uptake, and the ratio of gray matter uptake to white matter retention were compared among (11)C-PiB-positive, (11)C-PiB-equivocal, and (11)C-PiB-negative groups. RESULTS: Forty-three scans were visually assessed as (11)C-PiB-positive in both the static and the BP images. Ten scans were (11)C-PiB-equivocal in the static images. In 8 of them, the BP images were (11)C-PiB-positive, whereas the other 2 were (11)C-PiB-equivocal. Thirty-two scans were assessed as (11)C-PiB-negative in the static images. In the BP images, 4 were (11)C-PiB-positive and 2 were (11)C-PiB-equivocal. The mean gray matter uptake of (11)C-PiB in SUVR and nondisplaceable BP, respectively, showed statistically significant differences among the (11)C-PiB-positive, (11)C-PiB-equivocal, and (11)C-PiB-negative groups. The ratio of gray matter uptake to white matter retention was lower in the BP images than static images from the (11)C-PiB-negative and (11)C-PiB-equivocal groups, whereas it was higher in the (11)C-PiB-positive group. CONCLUSION: (11)C-PiB PET BP images can clarify visual interpretation of clinical static (11)C-PiB-equivocal images by reducing the interference of nonspecific white matter retention. We conclude that (11)C-PiB-equivocal PET findings on static images reflect cortical amyloid deposits, which can be verified using BP images. Furthermore, quantitative assessments, such as SUVR and nondisplaceable BP, are of no use for correctly rating equivocal visual findings.

Regional glucose metabolic reduction in dementia with Lewy bodies is independent of amyloid deposition.

PURPOSE: There is evidence that some cases of patients with dementia with Lewy bodies (DLB) can demonstrate Alzheimer disease (AD) like reduced glucose metabolism without amyloid deposition. The aim of this study was to clarify whether regional hypometabolism is related to amyloid deposits in the DLB brain and measure the degree of regional hypometabolism. METHODS: Ten consecutive subjects with DLB and 10 AD patients who underwent both Pittsburgh compound B (PiB)-PET and (18)F-fluoro-2-deoxyglucose (FDG)-PET were included in this study. Regional standardized uptake value ratio (SUVR)s normalised to cerebellar cortices were calculated in the FDG- and PiB-PET images. RESULTS: All AD patients and five DLB patients showed amyloid deposits (PiB positive). In the DLB group the parietotemporal and occipital metabolism were significantly lower than those in the AD group but there was no difference between the posterior cingulate hypometabolism between DLB and AD groups. There were no differences in regional glucose metabolism between PiB positive and negative DLB patients. CONCLUSIONS: In the DLB brain, it is suggested that decreased regional glucose metabolism is unrelated to amyloid deposits, although the hypometabolic area overlaps with the AD hypometabolic area and the degree of parietotemporal and occipital hypometabolism in DLB brain is much larger than that in AD brain.

Investigation of (11)C-PiB equivocal PET findings.

OBJECTIVE: We have encountered occasional equivocal findings when assessing cerebral cortical amyloid retention with (11)C-Pittsburgh compound B (PiB) PET. We investigated the diagnostic significance of equivocal PiB PET findings. METHODS: This retrospective study included 101 consecutive patients complaining of cognitive disorders (30 Alzheimer's disease, 25 mild cognitive impairment, 8 Lewy body disease, 7 frontotemporal lobar degeneration, 31 others) who underwent both (11)C-PiB PET and (18)F-fluorodeoxy-D-glucose (FDG) PET. We visually classified PiB-positive, PiB-equivocal or PiB-negative ratings according to cortical uptake. For quantitative assessments of PiB PET, standard uptake values referred to cerebellar cortex (SUVR) were calculated in regional template volume of interests (frontal, temporoparietal, precuneus/posterior cingulate cortex, cerebral white matter and cerebellar cortex). The results of visual assessment were compared with the regional and mean cortical SUVRs and cortical-to-white matter ratio of PiB uptake, as well as clinical and FDG PET findings. RESULTS: Among the 101 scans, 41 were PiB negative, 11 were PiB equivocal, and 49 were rated PiB positive in the visual assessments. The mean cortical SUVR and cortical-to-white matter ratio were 0.97 ± 0.07 and 0.57 ± 0.21 in PiB-negative, 1.51 ± 0.17 and 0.75 ± 0.06 in PiB equivocal and 2.10 ± 0.33 and 0.97 ± 0.11 in PiB-positive group, respectively. Nine of 11 subjects with PiB-equivocal findings had cognitive impairments and FDG distribution compatible with Alzheimer's disease or dementia with Lewy bodies. CONCLUSIONS: We considered equivocal visual findings on PiB PET equivalent to PiB-positive with slight cortical uptake. In addition, slight cortical amyloid deposits were considered to cause cerebral metabolic abnormality and cognitive impairment. Although mean cortical SUVR was more sensitive than visual assessment because of low cortical-to-white matter contrast due to non-specific accumulation in white matter, it is important not to overlook small amounts of cortical uptake of PiB in visual inspection for exact diagnosis.

Effects of angiotensin II receptor blocker on proteinuria in renal transplant recipients.

INTRODUCTION: Therapeutic approaches directed at reducing proteinuria are under development. The aim of the present study was to prospectively elucidate the impact of losartan treatment in renal transplant recipients with persistent proteinuria. PATIENTS AND METHODS: Twenty-eight patients with persistent proteinuria or mild hypertension were assigned to receive losartan. Proteinuria was defined as a ratio of urinary protein to urinary creatinine (U(P)/U(Cr)) >0.5 in continual urinary tests in the outpatient setting. RESULTS: All patients with mild hypertension reached target blood pressure (BP) with losartan treatment, but the change was not significant. In twelve patients with proteinuria before initiation of the study, urinary protein excretion was significantly reduced with treatment. No correlation was observed between reductions in proteinuria and mean BP. A significant decrease was identified in the hemoglobin concentration of patients with serum creatinine concentrations >2.0 mg/dl before the study. DISCUSSION: Losartan efficiently reduces proteinuria in renal transplant recipients with adequate tolerance. Multicentric prospective studies are required to confirm its clinical effectiveness.

[Cytomegalovirus infection in peptic ulcer in renal transplant recipient: a case report].

Gastroduodenal ulcers in renal transplant recipients are usually originated from excessive acid secretion or infection of Helicobacter pyroli. Herein, we report a case of cytomegalovirus (CMV)--induced gastric ulcer following cadaveric renal transplantation. The patient was a 48-year-old man with chronic renal failure and received cadaveric renal transplantation. A month later, he had epigastralgia without CMV-positive antigenemia and received gastrointestinal fiberscopy. Endoscopically, gastric ulcer was identified. Histological findings revealed conspicious nuclear enlargement of the non-epithelial cells in the ulcer bed, which indicated CMV infection. The patient was treated with ganciclovir for 2 weeks and the symptom was relieved. He discharged with a good renal function on day 75 posttransplant. CMV infection plays an important role in gastric ulcer after renal transplantation. Antigenemia assay dose not seem feasible for the detection of CMV-induced gastric ulcer.

Combined chemotherapy with gemcitabine and cisplatin for metastatic urothelial carcinomas in patients 80 years of age and over.

BACKGROUND: This retrospective study aimed to determine the efficacy and toxicity of a combined chemotherapeutic regimen of gemcitabine and cisplatin (GC) for the treatment of metastatic urothelial carcinomas (UCs) in patients 80 years of age and over. PATIENTS AND METHODS: Twelve patients who were at least 80 years old and had been diagnosed with metastatic UC were treated with GC. The patient cohort consisted of 9 men and 3 women, with a median age of 83 (range 80-84) years. The median follow-up was 54 (range 14-80) months. RESULTS: Five out of the 12 patients (42%) showed an objective response, with two achieving a clinically complete response and three a partial response with GC. The median time to progression was 6 months, and the median overall survival was 14 months. The grade 3 and 4 toxicities of the regimen were primarily hematological, including anemia (33%), neutropenia (58%), and thrombocytopenia (50%). No grade 3 or 4 non-hematological toxicities were found. CONCLUSION: GC appears to be an effective and well-tolerated regimen for the treatment of metastatic UCs in very old patients.

Gemcitabine and cisplatin for advanced urothelial carcinomas: the Ehime University Hospital experience.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of a combined chemotherapy regimen, gemcitabine and cisplatin (GC), in the treatment of advanced urothelial carcinomas. METHODS: Fifty-five patients with advanced urothelial cancer were treated with GC (gemcitabine 1000 mg/m(2) on days 1, 8, and 15; cisplatin 70 mg/m(2) on day 2) every 28 days. The median follow-up was 30 months (range, 3 to 57 months). RESULTS: With the GC therapy, 35 of the 55 patients (63.6%) showed an objective response, with 7 (12.7%) achieving a clinical complete response (CR) and 28 (50.9%), a partial response (PR). GC therapy had a better impact on metastases in the lung and lymph nodes than on metastases in the liver and bone. Lung and lymph nodes showed objective responses of 64.7% and 65.8%, respectively. Eight of the 20 patients (40.0%) who had previously been treated with other regimens showed an objective response, with 1 achieving a CR and 7 achieving a PR. In the 47 patients with metastasis, the median time to progression was 7.0 months (range, 2 to 49 months), and the median overall survival was 12.0 months (range, 3 to 49 months). The 2-year survival rate was 80.0% in the CR group, while it was 55.1% in the PR group and 10.0% in the progressive disease (PD) group. The toxicities associated with GC, particularly mucositis, anorexia, and alopecia, were quite mild. Grade 3-4 toxicity was primarily hematological, including anemia (27.3%), neutropenia (32.7%), and thrombocytopenia (43.6%). CONCLUSION: GC is considered to be a highly effective and well-tolerated regimen for the treatment of advanced urothelial carcinomas, with moderate toxicity.